Randomized Clinical Trials and Observational Tribulations: Providing Clinical Evidence for Personalized Surgical Pain Management Care Models

Ivo Abraham¹, Kai-Uwe Lewandrowski^{2

3

4}, John C Elfar⁵, Zong-Ming Li⁵, Rossano Kepler Alvim Fiorelli⁶, Mauricio G Pereira⁷, Morgan P Lorio⁸, Benedikt W Burkhardt⁹, Joachim M Oertel¹⁰, Peter A Winkler¹¹, Huilin Yang¹², Jorge Felipe Ramírez León¹³, Albert E Telfeian¹⁴, Álvaro Dowling¹⁵, Roth A A Vargas¹⁶, Ricardo Ramina¹⁷, Marjan Asefi¹⁸, Paulo Sérgio Teixeira de Carvalho¹⁹, Helton Defino¹⁵, Jaime Moyano²⁰, Nicola Montemurro²¹, Anthony Yeung²², Pietro Novellino²³, On Behalf Of Teams/Organizations/Institutions

Affiliations

¹ Pharmacy Medicine, and Clinical Translational Sciences, University of Arizona, Roy P. Drachman Hall, Rm. B306H, Tucson, AZ 85721, USA.
² Center for Advanced Spine Care of Southern Arizona, Tucson, AZ 85712, USA.
³ Department of Orthopaedics, Fundación Universitaria Sanitas, Bogotá 111321, Colombia.
⁴ Department of Orthopedics, Hospital Universitário Gaffre e Guinle, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro 20270-004, Brazil.
⁵ Department of Orthopaedic Surgery, College of Medicine-Tucson Campus, Health Sciences Innovation Building (HSIB), University of Arizona, 1501 N. Campbell Avenue, Tower 4, 8th Floor, Suite 8401, Tucson, AZ 85721, USA.
⁶ Department of General and Specialized Surgery, Gaffrée e Guinle University Hospital, Federal University of the State of Rio de Janeiro (UNIRIO), Rio de Janeiro 20270-004, Brazil.
⁷ Faculty of Medicine, University of Brasilia, Federal District, Brasilia 70919-900, Brazil.
⁸ Advanced Orthopaedics, 499 E. Central Pkwy, Ste. 130, Altamonte Springs, FL 32701, USA.
⁹ Wirbelsäulenzentrum/Spine Center-WSC, Hirslanden Klinik Zurich, Witellikerstrasse 40, 8032 Zurich, Switzerland.
¹⁰ Klinik für Neurochirurgie, Universität des Saarlandes, Kirrberger Straße 100, 66421 Homburg, Germany.
¹¹ Department of Neurosurgery, Charite Universitaetsmedizin Berlin, 13353 Berlin, Germany.
¹² Orthopaedic Department, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Suzhou 215031, China.
¹³ Minimally Invasive Spine Center Bogotá D.C. Colombia, Reina Sofía Clinic Bogotá D.C. Colombia, Department of Orthopaedics, Fundación Universitaria Sanitas, Bogotá 110141, Colombia.
¹⁴ Department of Neurosurgery, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
¹⁵ Department of Orthopaedic Surgery, University of São Paulo, Ribeirão Preto 14071-550, Brazil.
¹⁶ Department of Neurosurgery, Foundation Hospital Centro Médico Campinas, Campinas 13083-210, Brazil.
¹⁷ Neurological Institute of Curitiba, Curitiba 80230-030, Brazil.
¹⁸ Department of Biology, Nano-Biology, University of North Carolina, Greensboro, NC 27413, USA.
¹⁹ Pain and Spine Minimally Invasive Surgery Service, Gaffre e Guinle University Hospital, Rio de Janeiro 20270-004, Brazil.
²⁰ La Sociedad Iberolatinoamericana De Columna (SILACO), The Spine Committee of the Ecuadorian Society of Orthopaedics and Traumatology (Comité de Columna de la Sociedad Ecuatoriana de Ortopedia y Traumatología), Quito 170521, Ecuador.
²¹ Department of Neurosurgery, Azienda Ospedaliero Universitaria Pisana, University of Pisa, 56124 Pisa, Italy.
²² Desert Institute for Spine Care, Phoenix, AZ 85020, USA.
²³ Guinle and State Institute of Diabetes and Endocrinology, Rio de Janeiro 20270-004, Brazil.

PMID: 37511657
PMCID: PMC10381640
DOI: 10.3390/jpm13071044

Randomized Clinical Trials and Observational Tribulations: Providing Clinical Evidence for Personalized Surgical Pain Management Care Models

Ivo Abraham et al. J Pers Med. 2023.

. 2023 Jun 25;13(7):1044.

doi: 10.3390/jpm13071044.

Authors

Affiliations

¹ Pharmacy Medicine, and Clinical Translational Sciences, University of Arizona, Roy P. Drachman Hall, Rm. B306H, Tucson, AZ 85721, USA.
² Center for Advanced Spine Care of Southern Arizona, Tucson, AZ 85712, USA.
³ Department of Orthopaedics, Fundación Universitaria Sanitas, Bogotá 111321, Colombia.
⁴ Department of Orthopedics, Hospital Universitário Gaffre e Guinle, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro 20270-004, Brazil.
⁵ Department of Orthopaedic Surgery, College of Medicine-Tucson Campus, Health Sciences Innovation Building (HSIB), University of Arizona, 1501 N. Campbell Avenue, Tower 4, 8th Floor, Suite 8401, Tucson, AZ 85721, USA.
⁶ Department of General and Specialized Surgery, Gaffrée e Guinle University Hospital, Federal University of the State of Rio de Janeiro (UNIRIO), Rio de Janeiro 20270-004, Brazil.
⁷ Faculty of Medicine, University of Brasilia, Federal District, Brasilia 70919-900, Brazil.
⁸ Advanced Orthopaedics, 499 E. Central Pkwy, Ste. 130, Altamonte Springs, FL 32701, USA.
⁹ Wirbelsäulenzentrum/Spine Center-WSC, Hirslanden Klinik Zurich, Witellikerstrasse 40, 8032 Zurich, Switzerland.
¹⁰ Klinik für Neurochirurgie, Universität des Saarlandes, Kirrberger Straße 100, 66421 Homburg, Germany.
¹¹ Department of Neurosurgery, Charite Universitaetsmedizin Berlin, 13353 Berlin, Germany.
¹² Orthopaedic Department, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Suzhou 215031, China.
¹³ Minimally Invasive Spine Center Bogotá D.C. Colombia, Reina Sofía Clinic Bogotá D.C. Colombia, Department of Orthopaedics, Fundación Universitaria Sanitas, Bogotá 110141, Colombia.
¹⁴ Department of Neurosurgery, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
¹⁵ Department of Orthopaedic Surgery, University of São Paulo, Ribeirão Preto 14071-550, Brazil.
¹⁶ Department of Neurosurgery, Foundation Hospital Centro Médico Campinas, Campinas 13083-210, Brazil.
¹⁷ Neurological Institute of Curitiba, Curitiba 80230-030, Brazil.
¹⁸ Department of Biology, Nano-Biology, University of North Carolina, Greensboro, NC 27413, USA.
¹⁹ Pain and Spine Minimally Invasive Surgery Service, Gaffre e Guinle University Hospital, Rio de Janeiro 20270-004, Brazil.
²⁰ La Sociedad Iberolatinoamericana De Columna (SILACO), The Spine Committee of the Ecuadorian Society of Orthopaedics and Traumatology (Comité de Columna de la Sociedad Ecuatoriana de Ortopedia y Traumatología), Quito 170521, Ecuador.
²¹ Department of Neurosurgery, Azienda Ospedaliero Universitaria Pisana, University of Pisa, 56124 Pisa, Italy.
²² Desert Institute for Spine Care, Phoenix, AZ 85020, USA.
²³ Guinle and State Institute of Diabetes and Endocrinology, Rio de Janeiro 20270-004, Brazil.

PMID: 37511657
PMCID: PMC10381640
DOI: 10.3390/jpm13071044

Abstract

Proving clinical superiority of personalized care models in interventional and surgical pain management is challenging. The apparent difficulties may arise from the inability to standardize complex surgical procedures that often involve multiple steps. Ensuring the surgery is performed the same way every time is nearly impossible. Confounding factors, such as the variability of the patient population and selection bias regarding comorbidities and anatomical variations are also difficult to control for. Small sample sizes in study groups comparing iterations of a surgical protocol may amplify bias. It is essentially impossible to conceal the surgical treatment from the surgeon and the operating team. Restrictive inclusion and exclusion criteria may distort the study population to no longer reflect patients seen in daily practice. Hindsight bias is introduced by the inability to effectively blind patient group allocation, which affects clinical result interpretation, particularly if the outcome is already known to the investigators when the outcome analysis is performed (often a long time after the intervention). Randomization is equally problematic, as many patients want to avoid being randomly assigned to a study group, particularly if they perceive their surgeon to be unsure of which treatment will likely render the best clinical outcome for them. Ethical concerns may also exist if the study involves additional and unnecessary risks. Lastly, surgical trials are costly, especially if the tested interventions are complex and require long-term follow-up to assess their benefit. Traditional clinical testing of personalized surgical pain management treatments may be more challenging because individualized solutions tailored to each patient's pain generator can vary extensively. However, high-grade evidence is needed to prompt a protocol change and break with traditional image-based criteria for treatment. In this article, the authors review issues in surgical trials and offer practical solutions.

Keywords: clinical evidence; pain generators; personalized care models; surgical clinical trials.

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Conflict of interest statement

There was no formal funding by private, governmental, or commercial funders. The participating spine centers (Center For Advanced Spine Care of Southern Arizona—Tucson, Arizona; Desert Institute of Spine Care—Phoenix, Arizona; Department of Orthopaedics, Fundación Universitaria Sanitas—Bogotá, D.C., Colombia; Department of Neurosurgery and Orthopaedics at Hospital Universitário Gaffre e Guinle, Universidade Federal do Estado do Rio de Janeiro—Rio de Janeiro, Brazil; Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University; The American–British Cowdray Medical Center; Good Doctor Teun Teun Spine Hospital; Endoscopic Spine Clinic, Santiago, Chile; Department of Neurosurgery, Nanoori Hospital Gangnam Hospital; West China Hospital of Sichuan University supported, with their internal resources, the design and conduction of this study. They aided in the collection, analysis, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results. The authors declare no conflict of interest to the work presented herein, including no personal circumstances or interests that may be perceived as inappropriately influencing the representation or interpretation of the research data or professional information.

Figures

**Figure 1**
Difficulties, improvements, major errors, and benefits of randomized clinical trials (RCTs) of surgical interventions.

**Figure 2**
The main differences between observational trials (OTs) in comparison with randomized clinical trials (RCTs).

See this image and copyright information in PMC

References

1. Moher D., Schulz K.F., Altman D.G. The CONSORT Statement: Revised Recommendations for Improving the Quality of Reports of Parallel-Group Randomized Trials. Ann. Intern. Med. 2001;134:657–662. doi: 10.7326/0003-4819-134-8-200104170-00011. - DOI - PubMed
1. Naumann R.W. Re-evaluating “Success” as It Pertains to Surgical Trials. J. Minim. Invasive Gynecol. 2021;28:496–501. doi: 10.1016/j.jmig.2020.10.011. - DOI - PubMed
1. Bogduk N., Fraifeld E.M. Proof or consequences: Who shall pay for the evidence in pain medicine? Pain Med. 2010;11:1–2. doi: 10.1111/j.1526-4637.2009.00770.x. - DOI - PubMed
1. Joeris A., Knoll C., Kalampoki V., Blumenthal A., Gaskell G. Patient-reported outcome measurements in clinical routine of trauma, spine and craniomaxillofacial surgeons: Between expectations and reality: A survey among 1212 surgeons. BMJ Open. 2018;8:e020629. doi: 10.1136/bmjopen-2017-020629. - DOI - PMC - PubMed
1. Hansson-Hedblom A., Jonsson E., Fritzell P., Hagg O., Borgstrom F. The Association Between Patient Reported Outcomes of Spinal Surgery and Societal Costs: A Register Based Study. Spine. 2019;44:1309–1317. doi: 10.1097/BRS.0000000000003050. - DOI - PubMed

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Randomized Clinical Trials and Observational Tribulations: Providing Clinical Evidence for Personalized Surgical Pain Management Care Models

Affiliations

Randomized Clinical Trials and Observational Tribulations: Providing Clinical Evidence for Personalized Surgical Pain Management Care Models

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources